1,401 research outputs found
Impaired neural development in a zebrafish model for lowe syndrome
No full textLowe syndrome, which is characterized by defects in the central nervous system, eyes and kidneys, is caused by mutation of the phosphoinositide 5-phosphatase OCRL1. The mechanisms by which loss of OCRL1 leads to the phenotypic manifestations of Lowe syndrome are currently unclear, in part, owing to the lack of an animal model that recapitulates the disease phenotype. Here, we describe a zebrafish model for Lowe syndrome using stable and transient suppression of OCRL1 expression. Deficiency of OCRL1, which is enriched in the brain, leads to neurological defects similar to those reported in Lowe syndrome patients, namely increased susceptibility to heat-induced seizures and cystic brain lesions. In OCRL1-deficient embryos, Akt signalling is reduced and there is both increased apoptosis and reduced proliferation, most strikingly in the neural tissue. Rescue experiments indicate that catalytic activity and binding to the vesicle coat protein clathrin are essential for OCRL1 function in these processes. Our results indicate a novel role for OCRL1 in neural development, and support a model whereby dysregulation of phosphoinositide metabolism and clathrin-mediated membrane traffic leads to the neurological symptoms of Lowe syndrome. © The Author 2011. Published by Oxford University Press. All rights reserved
Wiseman, Lowe, and Salter at Collins Series
No full text(l to r) Executive Director of MSU\u27s Stennis Center for Government Marty Wiseman, Director of the George W. Bush Presidential Library Alan Lowe, and Journalist-in-Residence Sid Salter pose for a photograph after Lowe\u27s presentation
Crawford, Lowe and Holt at Collins Series
No full text(l to r) US Grant Association\u27s Aaron Crawford, Director of the George W. Bush Presidential Library Alan Lowe, and George W. Bush Presidential Library Archivist Bobby Holt pose for a photograph during the reception
Defining absolute environmental limits for the built environment
No full textThe question addressed is whether it is possible to define working limits on environmental impacts from the built environment in terms of global carrying capacity. The main focus is on energy-related impacts, since these are global and relatively well-understood. Four possible approaches to defining limits are explored: static equilibrium, asymptotic, integral of excess and planned future. The conclusions that emerge from this exploration are that global environmental constraints are very tight, but also that they are dynamically and strongly influenced by the trajectory of social and technological development over the coming century. Their use as the basis for practical, quantitative metrics of sustainability, therefore, involves a large measure of subjectivity. A fifth approach - the developmental approach - is identified, which instead of focusing on long-term external constraints to human activity, focuses instead on the internal, short- to medium-term dynamics of the built environment itself. It appears likely that the developmental approach, guided by qualitative conclusions from the analysis of global carrying capacity, is likely to be most fruitful
Heroes of peer review: Robert Lowe
No full textThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were mad
Collins Series Group
No full text(l to r) Bobby Holt, Marty Wiseman, Alan Lowe, Sid Salter, Frances Coleman, and Stephen Cunetto pose for a photograph after Lowe\u27s presentation
Grant Association at Collins Series
No full textStaff members of the US Grant Association and CPRC pose for a photograph with Lowe and Holt after Lowe\u27s presentation. (l to r) Elizabeth Coggins, Bobby Holt, John Marszalek, Alan Lowe, Mike Ballard, and Aaron Crawfor
Collins Series Group
No full text(l to r) Glen Berry, Debra Fairbrother, Bobby Holt, Marty Wiseman, Alan Lowe, Sid Salter, Frances Coleman, and Stephen Cunetto pose for a photograph after Lowe\u27s presentation
Biography of an ERP: Tracing the fabrication of a virtual object
No full textThis paper provides an account of the way Enterprise Resource Planning (ERP) systems change over time. These changes are conceptualised as a biographical accumulation that gives the specific ERP technology its present character, attributes and historicity. The paper presents empirics from the implementations of an ERP package within a single Australasian organisation. Changes to the ERP take place as a result of imperatives which arise during the implementations. Our research and evidence then extends to a different time and place where the new release of the ERP software was being ‘sold’ to client firms in the UK. We theorise our research through a lens based on ideas from ANT ( actor network theory) and the concept of biography. The paper seeks to contribute an additional theorization for ANT studies that places the focus on the technological object and frees it from the ties of the implementation setting. We contrast this approach with Dechow and Mouritsen’s (2005) path dependency. The research illustrates the opportunistic and contested fabrications of a technological object and emphasizes the stability as well as the fluidity of its techno-logic
Gender and the culture of the English alehouse in late Stuart England
No full textThe world of the alehouse and tavern in early modern England has generally been
regarded as primarily male, a view that was deeply embedded in the period itself.
This essay explores the place of women within the public house, in serving, buying
and consuming alcohol, and the unwritten conventions that underpinned social
practice. It argues that while some female customers matched their contemporary
image, as disorderly, immoral and dishonest, it was also possible for respectable
women to visit a tavern or alehouse without risking their good name, provided they
adhered to the conventions. Middling-sort and elite women might drink and dine in
London taverns with their husbands, or in mixed parties; throughout England married
couples, and mixed groups of young folk, might drink, dance, and socialise; marketwomen
might assemble at the end of the day, and chapwomen often lodged overnight.
And, at least in London, respectable women might enter a public house alone, by
day, without meeting disapproval. Many establishments provided private as well as
public rooms, and these created social spaces for female customers, couples and
mixed parties, serving different needs than those met within the main public space
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